title: Depletion of regulatory T cells by targeting folate receptor 4 enhances the potency of a GM-CSF-secreting tumor cell immunotherapy.
abstract: In this report, a Treg-depleting anti-FR4 antibody is combined with a GM-CSF-secreting tumor cell immunotherapy (GVAX) for treatment of melanoma-bearing animals. Median survival time (MST) of animals treated with GVAX was 41 days, compared to a MST of 32 days in untreated animals. Anti-FR4 monotherapy had no effect on MST. Combination of anti-FR4 and GVAX significantly prolonged MST to 55 days, suggesting that these two agents can function cooperatively. Combination therapy increased expression of IFN-γ and granzyme B by CD8 T cells. In contrast to anti-CD25-mediated Treg depletion, administration of anti-FR4 after GVAX did not reduce efficacy, suggesting that anti-FR4 does not deplete effector cells induced by GVAX. Triple combination of a blocking CTLA4 antibody with GVAX and anti-FR4 further enhanced overall survival and reduced growth of well-established melanomas. Considered together, anti-FR4 antibody and GVAX may be a promising approach for the treatment of patients with cancer.
authors.affiliation: Cell Genesys Inc, South San Francisco, CA 94080, USA. sliang@gmail.com
authors.forename: Spencer C
authors.initials: SC
authors.lastname: Liang
authors.forename: Marina
authors.initials: M
authors.lastname: Moskalenko
authors.forename: Melinda
authors.initials: M
authors.lastname: Van Roey
authors.forename: Karin
authors.initials: K
authors.lastname: Jooss
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000276:immunology; D045744:Cell Line, Tumor; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008545:Melanoma / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
chemical_list: D000906:Antibodies; D019496:Cancer Vaccines; D011956:Receptors, Cell Surface; C543634:folate receptor 4, mouse; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: Cancer immunotherapy; Costimulation; T cells; Tregs